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Timothy R. Rebbeck, Ph.D. Background: Women with mutations in the BRCA1/2 genes carry an increased risk for developing breast cancer. However, there is substantial variation in the incidence of breast cancer in BRCA1/2 mutation carriers. Other risk factors may include hormone related exposures, reproductive status such as age at first birth or never giving birth, and other genetic variations. The gene AIB1 was identified in a search of genes that are amplified in breast tumors. AIB1 enhanced estrogen-dependent gene transcription suggesting that altered expression of AIB1 may influence the progression of steroid-dependent cancers. As in some other hormone-related genes, AIB1 has a region that repeats three nucleotides (CAG) that code for the amino acid glutamine. The purpose of this study was to determine whether AIB1 variation was associated with BRCA1/2-associated breast cancers. Advance: A matched case-control study of 448 women with BRCA1/2 mutations was conducted. Women who had their first live birth at a later age or women who had never given birth had increases in BRCA1/2-associated breast cancer risk. Also, women with 28 or 29 polyglutamine repeats in AIB1 were at increased risk for BRCA1/2-associated breast cancer risk compared to women with genes with fewer polyglutamine repeats. Implications: These results support the idea that pathways that involve endocrine signaling, as measured by AIB1 genotype and reproductive history, may have a substantial role in BRCA1/2related breast cancer. The ability to effectively apply risk-prediction and reduction strategies in BRCA1/2 carriers may depend on the knowledge of additional risk factors in addition to BRCA1/2 mutation status. Publication: Rebbeck TR, Wang Y, Kantoff PW, Krithivas K, Neuhausen SL, Godwin AK, Daly MB, Narod SA, Brunet JS, Vesprini D, Garber JE, Lynch HT, Weber BL, Brown M. Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. Cancer Res. 2001 Jul 15;61(14):5420-4. |
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